ArticleScientific reports2019
Loss of the serine protease HTRA1 impairs smooth muscle cells maturation.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Blood vessel organoids generated by base editing and harboring single nucleotide variation in Notch3 effectively recapitulate CADASIL-related pathogenesis.Molecular neurobiology · 2024Article
- Proteome-Wide Genetic Investigation of Large Artery Stiffness.JACC. Basic to translational science · 2024Article
- Progress to Clarify HowBiomolecules · 2024Review
- Progress in the Study of the Role and Mechanism of HTRA1 in Diseases Related to Vascular Abnormalities.International journal of general medicine · 2024Review
- Elevated TGFβ signaling contributes to cerebral small vessel disease in mouse models of Gould syndrome.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Association BetweenPharmacogenomics and personalized medicine · 2023Article
- Novel mutations in HTRA1-related cerebral small vessel disease and comparison with CADASIL.Annals of clinical and translational neurology · 2022Article
- Proteolysis: a key post-translational modification regulating proteoglycans.American journal of physiology. Cell physiology · 2022Review
- Porphyromonas gingivalis-mediated disruption in spiral artery remodeling is associated with altered uterine NK cell populations and dysregulated IL-18 and Htra1.Scientific reports · 2022Article
- Interplay between HTRA1 and classical signalling pathways in organogenesis and diseases.Saudi journal of biological sciences · 2022Review
- Article
- Notch-ing up knowledge on molecular mechanisms of skin fibrosis: focus on the multifaceted Notch signalling pathway.Journal of biomedical science · 2021Review
- Cross-sectional associations among P3NP, HtrA, Hsp70, Apelin and sarcopenia in Taiwanese population.BMC geriatrics · 2021Article
- Isolation of Murine Primary Aortic Smooth Muscle Cells.Bio-protocol · 2021Article
- Potential Molecular Mechanism of theBioMed research international · 2020Article
- The Roles of TGF-β Signaling in Cerebrovascular Diseases.Frontiers in cell and developmental biology · 2020Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular smooth muscle cell (VSMC) dysfunction is a hallmark of small vessel disease, a common cause of stroke and dementia. Two of the most frequently mutated genes in familial small vessel disease are HTRA1 and NOTCH3. The protease HTRA1 cleaves the NOTCH3 ligand JAG1 implying a mechanistic link between HTRA1 and Notch signaling. Here we report that HTRA1 is essential for VSMC differentiation into the contractile phenotype. Mechanistically, loss of HTRA1 increased JAG1 protein levels and NOTCH3 signaling activity in VSMC. In addition, the loss of HTRA1 enhanced TGFβ-SMAD2/3 signaling activity. Activation of either NOTCH3 or TGFβ signaling resulted in increased transcription of the HES and HEY transcriptional repressors and promoted the contractile VSMC phenotype. However, their combined over-activation led to an additive accumulation of HES and HEY proteins, which repressed the expression of contractile VSMC marker genes. As a result, VSMC adopted an immature phenotype with impaired arterial vasoconstriction in Htra1-deficient mice. These data demonstrate an essential role of HTRA1 in vascular maturation and homeostasis by controlling Notch and TGFβ signaling.
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